1. Field of the Invention
The invention relates to novel 2-phenyl- and 2-benzyl-N-[(trichloromethyl)thio]succinimides having antifungal activity, to a method for their use as antifungal agents, and to antifungal compositions comprising them as active ingredients.
2. Description of the Prior Art
Fungicides find application as plant protectants, for the preservation of wood, leather, lacquer, textiles, paper and other organic materials, and in combating fungus infections in animals and man. Many of these fungicides, however, have certain disadvantages. Thus, organic mercury compounds are toxic, organic tin compounds are light sensitive, chlorophenols such as pentachlorophenol are volatile and toxic to man, and derivatives of dithiocarbamic acids react with metal siccatives in lacquers thus causing discoloration.
U.S. Pat. No. 2,553,770 discloses, as fungicides, germicides and insecticides, a class of N-[(trichloromethyl)thio] compounds represented by the general structural formula: ##STR2## WHERE R is defined as an organic residue which may be aliphatic, aromatic, alicyclic, heterocyclic and substituted derivatives of such organic residues. Exemplary of compounds disclosed are N-[(trichloromethyl)thio]imides of the following structures: ##STR3## Compounds I (captan), II (phaltan; folpet) and III are presently items of commerce. The mechanism of action of captan is apparently due to the blocking of the SH groups of phosphorylating enzymes, cf. R. G. Owens and H. M. Novotny, Contribs. Boyce Thompson Inst. 20, 171-90 (1959).
In addition to the (trichloromethyl)thio compounds, fluoro-dichlorothio compounds have also been developed as follows: ##STR4##
CA 55, 27196d (1961) [J. prakt. Chem. 12, 172-6 (1961)] describes the preparation of 2-anilino- and 2-(4-methylanilino)-N-[(trichloromethyl)thio]succinimide. There is no disclosure in this reference of antimicrobial activity.
CA 59, 9836e (1963) (German Pat. No. 1,145,420) describes the preparation of N[(trichloromethyl)thio]-.alpha.,.alpha.-pentamethylene-succinimide and its utility as a broad spectrum fungicide.
CA 69, P35497U (1968) (British Pat. No. 1,099,299) describes N-[(polyhaloalkyl)thio]alkenylsuccinimides, e.g., N-[(trichloromethyl)thio]-2-allylsuccinimide, having utility as fungicides.
None of the foregoing disclosed references describe or suggest N-[(trichloromethyl)thio]succinimides mono-substituted at the 2-position by phenyl or benzyl.
In the development of new fungicides, certain properties are desirable. Thus a fungicide should desirably meet all of the following criteria: (1) be innocuous to man, (2) have high activity of long duration, and (3) possess a broad spectrum of activity.
Since fungicides of the class of N-[(trichloromethyl)thio]dicarboximides fulfill the requirement of long duration of activity, extensive investigations have been carried out with the purpose of finding new compounds of that class which possess a broad spectrum of activity and which are innocuous to man. With respect to the latter, in recent years certain N-[(trichloromethyl)thio] compounds such as captan (I) and folpet (II) have become suspect as producing malformation-causing mutations, cf. "Umschau", 1970, p. 652 and P. Schulster, "Die Zeit", Jan. 4, 1974. Apparently the phthalimide structure of these fungicides is responsible for the detrimental effects. Thus the discovery of new compounds of this class which do not possess the phthalimide structure but which possess high fungicidal activity is of paramount importance.
It was found that of a large number of synthetically prepared compounds, by no means all compounds of the general structural formula ##STR5## as defined in U.S. Pat. No. 2,553,770 noted hereinabove display fungicidal activity. Rather, activity is associated with strictly defined structural features. Thus, the trichloromethylthio compounds obtained from anthracene-maleic anhydride adduct, caryophyllen-maleic anhydride adduct, isoeugenol-maleic anhydride adduct, homophthalic anhydride, camphoric anhydride, hexadecyl succinic anhydride and many other anhydrides are inactive.